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Hairy/enhancer-of-split related with YRPW motif protein 2 (HES-related repressor protein 2) (Hairy and enhancer of split-related protein 2) (HESR-2) (Hairy-related transcription factor 2) (HRT-2) (mHRT2) (Protein gridlock homolog)

 HEY2_MOUSE              Reviewed;         339 AA.
Q9QUS4; Q3TZ99; Q8CD44;
11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
10-OCT-2018, entry version 141.
RecName: Full=Hairy/enhancer-of-split related with YRPW motif protein 2;
AltName: Full=HES-related repressor protein 2;
AltName: Full=Hairy and enhancer of split-related protein 2;
Short=HESR-2;
AltName: Full=Hairy-related transcription factor 2;
Short=HRT-2;
Short=mHRT2;
AltName: Full=Protein gridlock homolog;
Name=Hey2; Synonyms=Chf1, Herp, Herp1, Hesr2, Hrt2;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL
STAGE.
PubMed=10588864; DOI=10.1006/dbio.1999.9454;
Nakagawa O., Nakagawa M., Richardson J.A., Olson E.N., Srivastava D.;
"HRT1, HRT2 and HRT3: a new subclass of bHLH transcription factors
marking specific cardiac, somitic and pharyngeal arch segments.";
Dev. Biol. 216:72-84(1999).
[2]
NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL
STAGE.
PubMed=10860664; DOI=10.1006/geno.2000.6200;
Steidl C., Leimeister C., Klamt B., Maier M., Nanda I., Dixon M.,
Clarke R., Schmid M., Gessler M.;
"Characterization of the human and mouse HEY1, HEY2, and HEYL genes:
cloning, mapping, and mutation screening of a new bHLH gene family.";
Genomics 66:195-203(2000).
[3]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND
DEVELOPMENTAL STAGE.
PubMed=10692439; DOI=10.1074/jbc.275.9.6381;
Chin M.T., Maemura K., Fukumoto S., Jain M.K., Layne M.D.,
Watanabe M., Hsieh C.-M., Lee M.-E.;
"Cardiovascular basic helix loop helix factor 1, a novel
transcriptional repressor expressed preferentially in the developing
and adult cardiovascular system.";
J. Biol. Chem. 275:6381-6387(2000).
[4]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=11486044; DOI=10.1128/MCB.21.17.6071-6079.2001;
Iso T., Sartorelli V., Chung G., Shichinohe T., Kedes L., Hamamori Y.;
"HERP, a new primary target of Notch regulated by ligand binding.";
Mol. Cell. Biol. 21:6071-6079(2001).
[5]
NUCLEOTIDE SEQUENCE [MRNA].
Kokubo H., Johnson R.L.;
"Cloning of hesr2 gene.";
Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J; TISSUE=Inner ear, and Testis;
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[7]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
DEVELOPMENTAL STAGE.
PubMed=10415358; DOI=10.1016/S0925-4773(99)00080-5;
Leimeister C., Externbrinck A., Klamt B., Gessler M.;
"Hey genes: a novel subfamily of hairy- and enhancer of split related
genes specifically expressed during mouse embryogenesis.";
Mech. Dev. 85:173-177(1999).
[9]
INDUCTION.
PubMed=10964718; DOI=10.1006/bbrc.2000.3354;
Maier M.M., Gessler M.;
"Comparative analysis of the human and mouse Hey1 promoter: Hey genes
are new Notch target genes.";
Biochem. Biophys. Res. Commun. 275:652-660(2000).
[10]
FUNCTION, DNA-BINDING, INDUCTION, AND MUTAGENESIS OF 49-ARG--ARG-61.
PubMed=11095750; DOI=10.1073/pnas.250485597;
Nakagawa O., McFadden D.G., Nakagawa M., Yanagisawa H., Hu T.,
Srivastava D., Olson E.N.;
"Members of the HRT family of basic helix-loop-helix proteins act as
transcriptional repressors downstream of Notch signaling.";
Proc. Natl. Acad. Sci. U.S.A. 97:13655-13660(2000).
[11]
FUNCTION, AND DEVELOPMENTAL STAGE.
PubMed=11160397;
Satow T., Bae S.-K., Inoue T., Inoue C., Miyoshi G., Tomita K.,
Bessho Y., Hashimoto N., Kageyama R.;
"The basic helix-loop-helix gene hesr2 promotes gliogenesis in mouse
retina.";
J. Neurosci. 21:1265-1273(2001).
[12]
FUNCTION, DNA-BINDING, AND INTERACTION WITH HDAC1; HES1; NCOR1 AND
SIN3A.
PubMed=11486045; DOI=10.1128/MCB.21.17.6080-6089.2001;
Iso T., Sartorelli V., Poizat C., Iezzi S., Wu H.-Y., Chung G.,
Kedes L., Hamamori Y.;
"HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling.";
Mol. Cell. Biol. 21:6080-6089(2001).
[13]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=12372253; DOI=10.1016/S0960-9822(02)01150-8;
Gessler M., Knobeloch K.-P., Helisch A., Amann K., Schumacher N.,
Rohde E., Fischer A., Leimeister C.;
"Mouse gridlock: no aortic coarctation or deficiency, but fatal
cardiac defects in Hey2 -/- mice.";
Curr. Biol. 12:1601-1604(2002).
[14]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=12372254; DOI=10.1016/S0960-9822(02)01149-1;
Donovan J., Kordylewska A., Jan Y.N., Utset M.F.;
"Tetralogy of fallot and other congenital heart defects in Hey2 mutant
mice.";
Curr. Biol. 12:1605-1610(2002).
[15]
INDUCTION, AND SUBCELLULAR LOCATION.
PubMed=11741889; DOI=10.1074/jbc.M110495200;
Iso T., Chung G., Hamamori Y., Kedes L.;
"HERP1 is a cell type-specific primary target of Notch.";
J. Biol. Chem. 277:6598-6607(2002).
[16]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=12454287; DOI=10.1073/pnas.252648999;
Sakata Y., Kamei C.N., Nakagami H., Bronson R., Liao J.K., Chin M.T.;
"Ventricular septal defect and cardiomyopathy in mice lacking the
transcription factor CHF1/Hey2.";
Proc. Natl. Acad. Sci. U.S.A. 99:16197-16202(2002).
[17]
FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
PubMed=12947105; DOI=10.1074/jbc.M300448200;
Sakamoto M., Hirata H., Ohtsuka T., Bessho Y., Kageyama R.;
"The basic helix-loop-helix genes Hesr1/Hey1 and Hesr2/Hey2 regulate
maintenance of neural precursor cells in the brain.";
J. Biol. Chem. 278:44808-44815(2003).
[18]
FUNCTION.
PubMed=15345511; DOI=10.1161/01.ATV.0000143936.77094.a4;
Sakata Y., Xiang F., Chen Z., Kiriyama Y., Kamei C.N., Simon D.I.,
Chin M.T.;
"Transcription factor CHF1/Hey2 regulates neointimal formation in vivo
and vascular smooth muscle proliferation and migration in vitro.";
Arterioscler. Thromb. Vasc. Biol. 24:2069-2074(2004).
[19]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=15297376; DOI=10.1161/01.RES.0000141136.85194.f0;
Kokubo H., Miyagawa-Tomita S., Tomimatsu H., Nakashima Y.,
Nakazawa M., Saga Y., Johnson R.L.;
"Targeted disruption of hesr2 results in atrioventricular valve
anomalies that lead to heart dysfunction.";
Circ. Res. 95:540-547(2004).
[20]
FUNCTION.
PubMed=15107403; DOI=10.1101/gad.291004;
Fischer A., Schumacher N., Maier M., Sendtner M., Gessler M.;
"The Notch target genes Hey1 and Hey2 are required for embryonic
vascular development.";
Genes Dev. 18:901-911(2004).
[21]
FUNCTION, INTERACTION WITH GATA4, AND MUTAGENESIS OF 33-SER--SER-37.
PubMed=15485867; DOI=10.1074/jbc.M409879200;
Kathiriya I.S., King I.N., Murakami M., Nakagawa M., Astle J.M.,
Gardner K.A., Gerard R.D., Olson E.N., Srivastava D., Nakagawa O.;
"Hairy-related transcription factors inhibit GATA-dependent cardiac
gene expression through a signal-responsive mechanism.";
J. Biol. Chem. 279:54937-54943(2004).
[22]
FUNCTION.
PubMed=15680351; DOI=10.1016/j.ydbio.2004.10.025;
Kokubo H., Miyagawa-Tomita S., Nakazawa M., Saga Y., Johnson R.L.;
"Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch
signaling in the developing cardiovascular system.";
Dev. Biol. 278:301-309(2005).
[23]
FUNCTION, INTERACTION WITH GATA4 AND GATA6, DEVELOPMENTAL STAGE, AND
DISRUPTION PHENOTYPE.
PubMed=16199874; DOI=10.1128/MCB.25.20.8960-8970.2005;
Fischer A., Klattig J., Kneitz B., Diez H., Maier M., Holtmann B.,
Englert C., Gessler M.;
"Hey basic helix-loop-helix transcription factors are repressors of
GATA4 and GATA6 and restrict expression of the GATA target gene ANF in
fetal hearts.";
Mol. Cell. Biol. 25:8960-8970(2005).
[24]
FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
PubMed=17332425; DOI=10.1161/01.RES.0000261693.13269.bf;
Koibuchi N., Chin M.T.;
"CHF1/Hey2 plays a pivotal role in left ventricular maturation through
suppression of ectopic atrial gene expression.";
Circ. Res. 100:850-855(2007).
[25]
FUNCTION, INTERACTION WITH HEYL, DEVELOPMENTAL STAGE, AND DISRUPTION
PHENOTYPE.
PubMed=17303760; DOI=10.1161/01.RES.0000260913.95642.3b;
Fischer A., Steidl C., Wagner T.U., Lang E., Jakob P.M., Friedl P.,
Knobeloch K.-P., Gessler M.;
"Combined loss of Hey1 and HeyL causes congenital heart defects
because of impaired epithelial to mesenchymal transition.";
Circ. Res. 100:856-863(2007).
[26]
FUNCTION, AND DEVELOPMENTAL STAGE.
PubMed=17259303; DOI=10.1242/dev.02777;
Kokubo H., Tomita-Miyagawa S., Hamada Y., Saga Y.;
"Hesr1 and Hesr2 regulate atrioventricular boundary formation in the
developing heart through the repression of Tbx2.";
Development 134:747-755(2007).
-!- FUNCTION: Transcriptional repressor which functions as a
downstream effector of Notch signaling in cardiovascular
development. Specifically required for the Notch-induced
endocardial epithelial to mesenchymal transition, which is itself
criticial for cardiac valve and septum development. May be
required in conjunction with HEY1 to specify arterial cell fate or
identity. Promotes maintenance of neuronal precursor cells and
glial versus neuronal fate specification. Binds preferentially to
the canonical E box sequence 5'-CACGTG-3'. Represses transcription
by the cardiac transcriptional activators GATA4 and GATA6 and by
the neuronal bHLH factors ASCL1/MASH1 and NEUROD4/MATH3.
{ECO:0000269|PubMed:10692439, ECO:0000269|PubMed:11095750,
ECO:0000269|PubMed:11160397, ECO:0000269|PubMed:11486045,
ECO:0000269|PubMed:12372253, ECO:0000269|PubMed:12372254,
ECO:0000269|PubMed:12454287, ECO:0000269|PubMed:12947105,
ECO:0000269|PubMed:15107403, ECO:0000269|PubMed:15297376,
ECO:0000269|PubMed:15345511, ECO:0000269|PubMed:15485867,
ECO:0000269|PubMed:15680351, ECO:0000269|PubMed:16199874,
ECO:0000269|PubMed:17259303, ECO:0000269|PubMed:17303760,
ECO:0000269|PubMed:17332425}.
-!- SUBUNIT: May self-associate (By similarity). Interacts with ARNT
(By similarity). Interacts with GATA4, GATA6, HES1 and HEYL.
Interacts with HDAC1, NCOR1 and SIN3A. {ECO:0000250,
ECO:0000269|PubMed:11486045, ECO:0000269|PubMed:15485867,
ECO:0000269|PubMed:16199874, ECO:0000269|PubMed:17303760}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00380, ECO:0000255|PROSITE-ProRule:PRU00981,
ECO:0000269|PubMed:11741889}.
-!- TISSUE SPECIFICITY: Highly expressed in the aorta, lower
expression detected in the heart, brain, kidney, lung, muscle,
ovary and testis. {ECO:0000269|PubMed:10588864,
ECO:0000269|PubMed:10692439, ECO:0000269|PubMed:10860664,
ECO:0000269|PubMed:12947105}.
-!- DEVELOPMENTAL STAGE: Expressed in the developing somites and the
ventricles of the heart. Expressed in the otic vesicles between
E8.5 and E10.5. Expressed in the myocardium of the ventricles at
E9.5 and in the atrioventricular cushions from E9.5 to E12.5. At
E10.5, strongly expressed in the spinal nerves, the cranial
ganglia and the telencephalon. At E11.5, expressed in the
craniofacial region of the distal part of the maxillary arch,
along the rostral mandibular arch and surrounding the lateral
nasal processes. Expressed in the midbrain-hindbrain boundary and
the posterior edge of the hand- and foot-paddle. Expressed in the
mediodorsal region of the telencephalon and the ventricular zone
of the ventral spinal cord at E12, then in the ventral region of
the telencephalon and the cortical plate at E15. Expression in the
heart is limited to the compact myocardial layer at E17.5. Also
expressed in the developing retina up to P5, at which point
expression decreases. {ECO:0000269|PubMed:10415358,
ECO:0000269|PubMed:10588864, ECO:0000269|PubMed:10692439,
ECO:0000269|PubMed:10860664, ECO:0000269|PubMed:11160397,
ECO:0000269|PubMed:12947105, ECO:0000269|PubMed:16199874,
ECO:0000269|PubMed:17259303, ECO:0000269|PubMed:17303760,
ECO:0000269|PubMed:17332425}.
-!- INDUCTION: By activation of the Notch signaling pathway.
{ECO:0000269|PubMed:10964718, ECO:0000269|PubMed:11095750,
ECO:0000269|PubMed:11741889}.
-!- DISRUPTION PHENOTYPE: Mice display a spectrum of cardiac
malformations including ventricular septal defects, tetralogy of
Fallot and tricuspid atresia. The penetrance of the cardiac
malformation phenotype varies according to the strain, suggesting
the presence of modifier genes. {ECO:0000269|PubMed:12372253,
ECO:0000269|PubMed:12372254, ECO:0000269|PubMed:12454287,
ECO:0000269|PubMed:15297376, ECO:0000269|PubMed:16199874,
ECO:0000269|PubMed:17303760, ECO:0000269|PubMed:17332425}.
-!- SIMILARITY: Belongs to the HEY family. {ECO:0000305}.
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EMBL; AF172287; AAF14546.1; -; mRNA.
EMBL; AJ271867; CAB71346.1; -; mRNA.
EMBL; AF173902; AAF20174.1; -; mRNA.
EMBL; AF232240; AAF37298.1; -; mRNA.
EMBL; AB093589; BAC55066.1; -; mRNA.
EMBL; AK031506; BAC27428.1; -; mRNA.
EMBL; AK158000; BAE34310.1; -; mRNA.
EMBL; BC103575; AAI03576.1; -; mRNA.
EMBL; BC103576; AAI03577.1; -; mRNA.
CCDS; CCDS23766.1; -.
RefSeq; NP_038932.1; NM_013904.1.
UniGene; Mm.103573; -.
ProteinModelPortal; Q9QUS4; -.
SMR; Q9QUS4; -.
BioGrid; 200283; 1.
IntAct; Q9QUS4; 2.
STRING; 10090.ENSMUSP00000019924; -.
PhosphoSitePlus; Q9QUS4; -.
PaxDb; Q9QUS4; -.
PRIDE; Q9QUS4; -.
Ensembl; ENSMUST00000019924; ENSMUSP00000019924; ENSMUSG00000019789.
GeneID; 15214; -.
KEGG; mmu:15214; -.
UCSC; uc007etp.1; mouse.
CTD; 23493; -.
MGI; MGI:1341884; Hey2.
eggNOG; KOG4304; Eukaryota.
eggNOG; ENOG4111F0X; LUCA.
GeneTree; ENSGT00700000104130; -.
HOGENOM; HOG000286035; -.
HOVERGEN; HBG003275; -.
InParanoid; Q9QUS4; -.
KO; K09091; -.
OMA; STCASQR; -.
OrthoDB; EOG091G0HNC; -.
PhylomeDB; Q9QUS4; -.
TreeFam; TF323617; -.
PRO; PR:Q9QUS4; -.
Proteomes; UP000000589; Chromosome 10.
Bgee; ENSMUSG00000019789; Expressed in 265 organ(s), highest expression level in cardiac ventricle.
CleanEx; MM_HEY2; -.
ExpressionAtlas; Q9QUS4; baseline and differential.
Genevisible; Q9QUS4; MM.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0016580; C:Sin3 complex; IEA:Ensembl.
GO; GO:0005667; C:transcription factor complex; ISS:MGI.
GO; GO:0017053; C:transcriptional repressor complex; ISO:MGI.
GO; GO:0003677; F:DNA binding; IMP:UniProtKB.
GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
GO; GO:0035939; F:microsatellite binding; IDA:UniProtKB.
GO; GO:0046982; F:protein heterodimerization activity; IDA:MGI.
GO; GO:0042803; F:protein homodimerization activity; IDA:MGI.
GO; GO:0001102; F:RNA polymerase II activating transcription factor binding; ISO:MGI.
GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; ISO:MGI.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
GO; GO:0000983; F:transcription factor activity, RNA polymerase II core promoter sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0008134; F:transcription factor binding; IPI:MGI.
GO; GO:0009948; P:anterior/posterior axis specification; IGI:MGI.
GO; GO:0060842; P:arterial endothelial cell differentiation; IGI:BHF-UCL.
GO; GO:0060840; P:artery development; IGI:MGI.
GO; GO:0035910; P:ascending aorta morphogenesis; IMP:BHF-UCL.
GO; GO:0060413; P:atrial septum morphogenesis; IMP:BHF-UCL.
GO; GO:0003171; P:atrioventricular valve development; IMP:MGI.
GO; GO:0001568; P:blood vessel development; IGI:MGI.
GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IMP:BHF-UCL.
GO; GO:0003214; P:cardiac left ventricle morphogenesis; IMP:BHF-UCL.
GO; GO:0003300; P:cardiac muscle hypertrophy; IMP:MGI.
GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IDA:MGI.
GO; GO:0003215; P:cardiac right ventricle morphogenesis; IMP:BHF-UCL.
GO; GO:0060411; P:cardiac septum morphogenesis; IMP:BHF-UCL.
GO; GO:0060948; P:cardiac vascular smooth muscle cell development; IMP:MGI.
GO; GO:0003208; P:cardiac ventricle morphogenesis; IMP:UniProtKB.
GO; GO:0045165; P:cell fate commitment; IMP:MGI.
GO; GO:0090102; P:cochlea development; IMP:MGI.
GO; GO:0060977; P:coronary vasculature morphogenesis; IMP:MGI.
GO; GO:0035912; P:dorsal aorta morphogenesis; IGI:BHF-UCL.
GO; GO:0003199; P:endocardial cushion to mesenchymal transition involved in heart valve formation; IGI:MGI.
GO; GO:0060347; P:heart trabecula formation; IMP:BHF-UCL.
GO; GO:0060716; P:labyrinthine layer blood vessel development; IGI:BHF-UCL.
GO; GO:0014031; P:mesenchymal cell development; IMP:BHF-UCL.
GO; GO:0003150; P:muscular septum morphogenesis; IMP:BHF-UCL.
GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:MGI.
GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL.
GO; GO:0045746; P:negative regulation of Notch signaling pathway; IDA:BHF-UCL.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
GO; GO:2000820; P:negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation; IDA:BHF-UCL.
GO; GO:0060633; P:negative regulation of transcription initiation from RNA polymerase II promoter; ISO:MGI.
GO; GO:2000678; P:negative regulation of transcription regulatory region DNA binding; IDA:BHF-UCL.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0061314; P:Notch signaling involved in heart development; IC:BHF-UCL.
GO; GO:0007219; P:Notch signaling pathway; IDA:UniProtKB.
GO; GO:0003151; P:outflow tract morphogenesis; IMP:BHF-UCL.
GO; GO:0007389; P:pattern specification process; IMP:MGI.
GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IMP:MGI.
GO; GO:0010460; P:positive regulation of heart rate; IMP:MGI.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
GO; GO:0065004; P:protein-DNA complex assembly; IDA:MGI.
GO; GO:0061156; P:pulmonary artery morphogenesis; IMP:BHF-UCL.
GO; GO:0003184; P:pulmonary valve morphogenesis; IMP:BHF-UCL.
GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
GO; GO:0045607; P:regulation of inner ear auditory receptor cell differentiation; IGI:MGI.
GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:MGI.
GO; GO:2001212; P:regulation of vasculogenesis; IGI:BHF-UCL.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0003195; P:tricuspid valve formation; IMP:MGI.
GO; GO:0003186; P:tricuspid valve morphogenesis; IMP:BHF-UCL.
GO; GO:0036304; P:umbilical cord morphogenesis; IGI:BHF-UCL.
GO; GO:0001570; P:vasculogenesis; IGI:MGI.
GO; GO:0055015; P:ventricular cardiac muscle cell development; IMP:BHF-UCL.
GO; GO:0060412; P:ventricular septum morphogenesis; IMP:BHF-UCL.
GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IGI:MGI.
CDD; cd00083; HLH; 1.
Gene3D; 4.10.280.10; -; 1.
InterPro; IPR011598; bHLH_dom.
InterPro; IPR036638; HLH_DNA-bd_sf.
InterPro; IPR003650; Orange_dom.
Pfam; PF07527; Hairy_orange; 1.
Pfam; PF00010; HLH; 1.
SMART; SM00353; HLH; 1.
SMART; SM00511; ORANGE; 1.
SUPFAM; SSF47459; SSF47459; 1.
PROSITE; PS50888; BHLH; 1.
PROSITE; PS51054; ORANGE; 1.
1: Evidence at protein level;
Complete proteome; Developmental protein; DNA-binding;
Notch signaling pathway; Nucleus; Reference proteome; Repressor;
Transcription; Transcription regulation.
CHAIN 1 339 Hairy/enhancer-of-split related with YRPW
motif protein 2.
/FTId=PRO_0000245516.
DOMAIN 48 103 bHLH. {ECO:0000255|PROSITE-
ProRule:PRU00981}.
DOMAIN 122 157 Orange. {ECO:0000255|PROSITE-
ProRule:PRU00380}.
REGION 47 116 Transcriptional repression and
interaction with NCOR1 and SIN3A.
{ECO:0000269|PubMed:11486045}.
MOTIF 329 332 YQPW motif.
COMPBIAS 175 191 His-rich.
COMPBIAS 262 304 Ala-rich.
MUTAGEN 33 37 Missing: Abrogates interaction with GATA4
and repression of GATA4-mediated
transcription.
{ECO:0000269|PubMed:15485867}.
MUTAGEN 49 61 RKKRRGIIEKRRR->LE: Abrogates DNA-binding
and transcriptional repression.
{ECO:0000269|PubMed:11095750}.
CONFLICT 7 7 E -> K (in Ref. 6; BAC27428).
{ECO:0000305}.
CONFLICT 284 284 G -> E (in Ref. 6; BAE34310).
{ECO:0000305}.
SEQUENCE 339 AA; 35873 MW; 105BEEA06DE50444 CRC64;
MKRPCEETTS ESDLDETIDV GSENNYPGHA TSSVMRSNSP TTTSQIMARK KRRGIIEKRR
RDRINNSLSE LRRLVPTAFE KQGSAKLEKA EILQMTVDHL KMLQATGGKG YFDAHALATD
FMSIGFRECL TEVARYLSSV EGLDPSDPLR VRLVSHLSTC ASQREAAVMT SSMAHHHHPL
HPHHWAAAFH HLPTALLQPN GLHTSESTPC RLSTSSEVPS AHGSALLTAT FAHADSALRM
PSGGTVAPCV PPLSTSLLSL SATVHAAAAA ATAAAHSFPL SFAGAFPMLP SNAAAAAAVA
AATAISPPLS VSAASSPQQT STGTNNKPYQ PWGTEVGAF


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